Gestation-associated changes in the glycosylation of placental insulin and insulin-like growth factor receptors

• Gestational changes in the content of N-glycans on IR and IGFRs were found.
• Less total fucose (Fuc), less core Fuc, less α2,6-sialic acid (Sia) on IR through gestation.
• Less total Fuc, more core Fuc, less α2,6-Sia on IGF1R through gestation.
• More total Fuc, more core Fuc, unaltered α2,6-Sia on IGF2R through gestation.

IntroductionInsulin receptor (IR) and type 1 and type 2 insulin-like growth factor receptors (IGF1R and IGF2R) play important roles in regulation of placental and foetal growth. All three receptors are abundantly glycosylated. N-glycosylation significantly affects protein conformation and may alter its function. We have recently found that the N-glycome of placental membrane proteins alters during gestation. The aim of the study presented herein was to investigate whether there were gestation-related changes in N-glycan profiles of placental IR and IGFRs.MethodsPlacentas from healthy women at first (FTP) and third trimester (TTP) of pregnancy were collected, membrane proteins isolated, solubilised and used as the source of IR and IGFRs. Reactivity of glycoforms of IR and IGFRs with lectins was monitored by measuring radioactivity of 125I-ligands-receptors complexes.ResultsSignificant differences in the binding pattern of all three receptors to the lectins were observed between FTP and TTP, which suggest gestational changes in N-glycans bound to receptors. These changes include decrease in total fucosylated, core-fucosylated biantennary N-glycan (NA2F) and α2,6-sialo-N-glycans (for IR); decrease in total fucosylated and α2,6-sialo-N-glycans and an increase in NA2F N-glycans (for IGF1R) and an increase in the total fucosylation and NA2F N-glycans (for IGF2R).DiscussionThe gestational alterations in N-glycans attached to IR and IGFRs may represent a mechanism by which these receptors acquire new/additional roles as gestation progresses.